The immune tissues in the mucosal tissues such as the enteric canal, nasal cavity, oral cavity, respiratory organs, etc., which cover the interface with the external world in the animal body, form an immune system (i.e. mucosal immune system) which is independent of but shares a common mechanism with the immune system (i.e. the systemic immune system), which consists mainly of the spleen and bone marrow.
Among the mucosal tissues, the intestinal tract is not only a digestive organ which digests and absorbs food taken in from outside of the body but also a first line of defense being exposed to various foreign matters from outside of the body. Therefore, the intestinal tract contains abundant immune tissues. The mucosal immune system in the intestinal tract with a surface area spanning about 400 m2, in humans, consists of the gut-associated lymphoid tissues (GALTs), the largest immune tissue in the body, in which 60 to 70% of the body's lymphocytes reside, including Peyer's patches, mesenteric lymph nodes, intraepithelial lymphocytes, cryptopatches, etc.
Especially Peyer's patches located in the lamina propria mucosae in the small intestine play a role as the control tower directing whether immune responses are induced or, conversely, immunological tolerance is induced to various antigens absorbed through intestinal epithelium. Dendritic cells play an important role in the function of Peyer's patches.
As mucosal immune mechanisms as described above have been elucidated one after another, mucosal immune vaccines taking advantage of the mucosal immunity has been developed (Japanese Laid-Open Application No.2003-321392). The mucosal immune vaccine works such that, by transmucosal administration of antigens to the oral cavity or nasal cavity, secretory IgA antibodies are produced in fluid such as saliva from mucosal systems, while blood-serum derived IgG antibodies are produced in fluid such as gingival crevicular fluid from systemic tissues. Thus, the mucosal immune vaccine can induce immune responses both in the mucosal system and in the systemic system by transmucosal administration of antigens.
As an experimental attempt of such immune induction using mucosal immunity, it has been reported that, by nasal administration of a cell membrane protein of Haemophilus influenzae to mice as an antigen, IgA antibodies and IgG antibodies were produced in nasal washes and in serum, respectively, and as a result, immune responses were induced both in the mucosal system and in the systemic system (Yamamoto, M. et al. (1998) J. Immune. 161 (8):4115-4121). Further, it has also been reported that by nasal administration of envelope proteins of Streptococcus mutants to mice, immune responses were induced both in the mucosal system and in the systemic system (Saito, M. et al. (2001) J. Infect. Dis. 183 (5):823-826). Such mucosal immune vaccines, which are capable of inducing immune responses both in the mucosal system and in the systemic system to pathogenic microorganisms, show promise as a new type of vaccines for clinical application.